The overall goals of this project are to determine and compare the effects of morphine-like drugs and barbiturates on the cholinergic system in the brain. The present emphasis is on the effects of barbiturates on ACh release and the development of tolerance to pentobarbital in vivo and in vitro. Completed work has shown that several barbiturates inhibit K ion-stimulated ACh release in vitro; their ED's are generally in proportion to their effective lipid-water partition coefficients. Some in vivo tolerance to the hypnotic effects of pentobarbital has been developed by daily injections of a suspension of the drug. Proposed studies for the following year include further study of the time course and degree of tolerance development to the hypnotic effect and other behavioral effects of pentobarbital and correlation of the in vivo tolerance with changes in in vitro effects of the drug after chronic drug administration in vivo.